In conclusion, our results demonstrate that suppressing hepatic UGT1A1 with GNUR increases plasma bilirubin levels, lowers the bilirubin catabolized product urobilin that is absorbed from the gut, reverses hepatic steatosis, and improves fasting hyperglycemia and hyperinsulinemia in a mouse model of established dietary-induced obesity and NAFLD. Here, UGT1A1 is linked to metabolic dysfunction-associated steatotic liver disease.